Abstract
S-equol is a major bacterial metabolite of the soy isoflavone daidzein. It is known to be a phytoestrogen that acts by binding to the nuclear estrogen receptors (ERs) that are expressed in various brain regions, including the cerebellum. However, the effects of S-equol on cerebellar development and function have not yet been extensively studied. In this study, the effects of S-equol were evaluated using a mouse primary cerebellar culture, Neuro-2A clonal cells, and an astrocyte-enriched culture. S-equol augmented the dendrite arborization of Purkinje cells induced by triiodothyronine (T3) and the neurite growth of Neuro-2A cell differentiation. Such augmentation was suppressed by G15, a selective G-protein coupled ER (GPR30) antagonist, and ICI 182,780, an antagonist for ERs in both cultures. On the other hand, in astrocytes, S-equol induced cell proliferation and cell migration with an increase in the phosphorylated extracellular-signal-regulated kinase 1/2 and F-actin rearrangements. Such effects were suppressed by G15, but not by ICI. These findings indicated that S-equol may enhanced cerebellar development by affecting both neurons and astrocytes through several signaling pathways, including GPR30 and ERs. We here report a novel mechanism of S-equol in cerebellar development that may provide a novel possibility to use S-equol supplementation during development.
Highlights
S-equol [(S)-3-(4-hydroxyphenyl) chroman-7-ol] is a major metabolite of the soy isoflavone daidzein
We examined the effect of S-equol in the primary cerebellar culture
We found that S-equol augmented dendritogenesis, neuritogenesis, proliferation, and migration
Summary
S-equol [(S)-3-(4-hydroxyphenyl) chroman-7-ol] is a major metabolite of the soy isoflavone daidzein. It is exclusively produced by intestinal bacteria in response to soy isoflavone intake in some, but not all, humans [1,2]. S-equol has estrogenic activity and binds more tightly to estrogen receptor β (ERβ) than to ERα [2,3]. The induction of transcription by S-equol is more potent with ERα than with ERβ in various cell lines [4]. The natural S-equol supplement SES-5OH stimulates estrogenic transcriptional activity and the proliferation of MCF-7-E10 cells. Neither S-equol nor SES-5OH promotes the progression of implanted breast cancer cells (MCF-7-E10) in ovariectomized mice [7]. It is necessary to clarify this mechanism so that it can be employed as an effective pharmaceutical or nutraceutical agent
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